Progressive Increase of the Mutated Mitochondrial DNA Fraction in Kearns-Sayre Syndrome
Abstract
We have performed morphologic and biochemical studies in three pediatric cases of Kearns-Sayre syndrome. All cases had heteroplasmy with a high percentage of mitochondrial DNA (mtDNA) with deletion in muscle. The deletions were mapped to the same region of mtDNA but were of different sizes. The same type of deletion could also be detected in fibroblasts from all cases but the percentage was considerably lower. In two cases, an increase with time of the mutated mtDNA fraction in muscle was found and this increase paralleled the progression of the disease. Oximetric evaluation of respiratory-chain function in isolated muscle mitochondria showed a complex I deficiency in one case and was normal in the two other cases. Comparison of the fractional concentration of mtDNA with deletion in muscle and isolated mitochondria showed that the isolated mitochondria were not representative of the mitochondrial population in muscle. Mitochondria with high percentage of mtDNA with deletion were selectively lost. The finding of different mitochondrial populations is in good agreement with the morphology. One case spontaneously recovered from an infantile sideroblastic anemia before the development of Kearns-Sayre syndrome. The anemia was of the same type as that in Pearson's syndrome, a mitochondrial disorder with high amounts of mtDNA with deletion in blood cells. These findings indicate that the phenotype of a mtDNA deletion disorder can change with time and is governed by the fractional co…
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The tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency, accumulation of abnormally appearing mitochondria, and progressively deteriorating respiratory chain function in skeletal muscle.
“These tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency (1), accumulation of abnormally appearing mitochondria (23), and progressively deteriorating respiratory chain function in skeletal muscle (24,25).”
From Increased mitochondrial mass in mitochondrial myopathy mice (2002) · cites this paper as [24]
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Chrétien, D., Bourgeron, T., Rötig, A., Munnich, A., & Rustin, P. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)81016-2 · Cited by 65 · see citing works
Mitochondrial ATP-Synthase Deficiency in a Child with 3-Methylglutaconic Aciduria
Holme, E., Greter, J., Jacobson, C.-E., Larsson, N., Lindstedt, S., Nilsson, K. O., Oldfors, A., & Tulinius, M. (1992) · Pediatric Research · doi:10.1203/00006450-199212000-00022 · Cited by 64 · see citing works
Self-citationMitochondrial DNA disease and developmental implications for reproductive strategies
Burgstaller, J. P., Johnston, I. G., & Poulton, J. (2014) · Molecular Human Reproduction · doi:10.1093/molehr/gau090 · Cited by 62 · see citing works
Congenital neutropenia and primary immunodeficiency diseases
Spoor, J., Farajifard, H., & Rezaei, N. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.10.003 · Cited by 62 · see citing works
- Authors
- Larsson, N.-G., Holme, E., Kristiansson, B., Oldfors, A., & Tulinius, M.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Venue
- Pediatric Research
- Published
- 1990-08
- Volume
- 28
- Issue
- 2
- Pages
- 131-136
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2022312470
- Cited by
- 324
- References
- 6
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 3 · 2014: 10 · 2013: 7 · 2012: 4
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bernadotte Foundation For Children’s Eyecare
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Kearns-Sayre syndrome, mitochondrial DNA deletions, heteroplasmy, muscle mitochondria, disease progression, Pearson syndrome, fibroblasts
- MeSH terms
- Adolescent, Adult, Bone Marrow, Chromosome Deletion, Chromosome Mapping, DNA, Mitochondrial, Female, Humans, Kearns-Sayre Syndrome, Male, Mitochondria, Muscle, Mutation, Ophthalmoplegia, Time Factors
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